Genetic Variant NM_002153.3:c.803-3258T>C (chr16-82094817-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_002153.3(HSD17B2):c.803-3258T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.566 in 151,982 control chromosomes in the GnomAD database, including 24,603 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.57 ( 24603 hom., cov: 31)

Exomes 𝑓: 0.25 ( 0 hom. )

Consequence

HSD17B2
NM_002153.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.876

Publications

3 publications found

Variant links:

Genes affected

HSD17B2 (HGNC:5211): (hydroxysteroid 17-beta dehydrogenase 2) Enables estradiol 17-beta-dehydrogenase activity and testosterone dehydrogenase (NAD+) activity. Involved in response to retinoic acid. Predicted to be located in endoplasmic reticulum membrane. [provided by Alliance of Genome Resources, Apr 2022]

HSD17B2 links:

HSD17B2-AS1 (HGNC:56281): (HSD17B2 antisense RNA 1)

HSD17B2-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.611 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002153.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HSD17B2	NM_002153.3	MANE Select	c.803-3258T>C		intron	N/A	NP_002144.1	P37059

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
HSD17B2	ENST00000199936.9	TSL:1 MANE Select	c.803-3258T>C	intron	N/A	ENSP00000199936.4	P37059
HSD17B2	ENST00000566838.2	TSL:2	c.*3641T>C	3_prime_UTR	Exon 3 of 3	ENSP00000456471.1	H3BRZ6
HSD17B2	ENST00000891334.1		c.803-3258T>C	intron	N/A	ENSP00000561393.1

Frequencies

GnomAD3 genomes

AF:

0.566

AC:

85980

AN:

151860

Hom.:

24593

Cov.:

show subpopulations

Gnomad AFR

AF:

0.506

Gnomad AMI

AF:

0.604

Gnomad AMR

AF:

0.504

Gnomad ASJ

AF:

0.693

Gnomad EAS

AF:

0.561

Gnomad SAS

AF:

0.470

Gnomad FIN

AF:

0.566

Gnomad MID

AF:

0.699

Gnomad NFE

AF:

0.615

Gnomad OTH

AF:

0.593

GnomAD4 exome

AF:

0.250

AC:

AN:

Hom.:

Cov.:

AF XY:

0.250

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.500

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.566

AC:

86010

AN:

151978

Hom.:

24603

Cov.:

AF XY:

0.561

AC XY:

41643

AN XY:

74276

show subpopulations

African (AFR)

AF:

0.505

AC:

20940

AN:

41440

American (AMR)

AF:

0.504

AC:

7691

AN:

15262

Ashkenazi Jewish (ASJ)

AF:

0.693

AC:

2403

AN:

3470

East Asian (EAS)

AF:

0.562

AC:

2905

AN:

5170

South Asian (SAS)

AF:

0.472

AC:

2267

AN:

4804

European-Finnish (FIN)

AF:

0.566

AC:

5985

AN:

10566

Middle Eastern (MID)

AF:

0.690

AC:

203

AN:

294

European-Non Finnish (NFE)

AF:

0.616

AC:

41828

AN:

67954

Other (OTH)

AF:

0.587

AC:

1238

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1884

3768

5653

7537

9421

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

742

1484

2226

2968

3710

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.599

Hom.:

108111

Bravo

AF:

0.561

Asia WGS

AF:

0.470

AC:

1633

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

(source)

DANN

Benign

0.80

PhyloP100

0.88

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over